Organ-on-a-Chip Approach for Accelerating Blood-Brain Barrier Nanoshuttle Discovery

Area of Science:

• Biomedical Engineering
• Pharmacology
• Vascular Biology

Background:

• Organ-on-a-chip platforms offer dynamic simulation of in vivo vasculature.
• Traditional in vitro models like transwells have limitations in assessing vascular-targeted drug delivery systems (DDS).
• The blood-brain barrier (BBB) presents a significant challenge for drug delivery due to its complex endothelial structure.

Purpose of the Study:

• To evaluate the efficacy of an organ-on-a-chip BBB model in screening vascular-targeted DDS.
• To compare the performance of the BBB chip against a conventional transwell model.
• To identify novel nanoshuttles with enhanced blood-brain barrier penetration capabilities.

Main Methods:

• Development and utilization of a novel organ-on-a-chip system simulating the BBB.
• Comparative screening of drug delivery systems using the BBB chip and a transwell model.
• In vivo validation of nanoshuttles identified through the BBB chip screening.

Main Results:

• The BBB chip demonstrated superior performance in identifying functional vascular-targeted DDS compared to the transwell model.
• Nanoshuttles discovered using the BBB chip exhibited enhanced in vivo efficacy.
• The BBB chip accurately recapitulates the endothelial glycocalyx and its dynamics under shear stress, crucial for transport.

Conclusions:

• Organ-on-a-chip technology is a reliable and effective platform for screening vascular-targeted DDS.
• The BBB chip's ability to mimic the endothelial glycocalyx enhances the identification of efficient transendothelial transport strategies.
• This technology holds significant promise for advancing drug delivery research, particularly for brain-targeted therapies.